Phase 1/2 trial of talazoparib in combination with temozolomide in children and adolescents with refractory/recurrent solid tumors including Ewing sarcoma: A Children's Oncology Group Phase 1 Consortium study (ADVL1411).

ABSTRACT:

Purpose

We conducted a phase 1/2 trial of the poly(ADP-ribose) polymerase 1/2 inhibitor talazoparib in combination with low-dose temozolomide (TMZ) to determine the dose-limiting toxicities (DLTs), recommended phase 2 dose (RP2D), and pharmacokinetics of this combination in children with recurrent/refractory solid tumors; and to explore clinical activity in Ewing sarcoma (EWS) (NCT02116777).

Methods

Talazoparib (400-600 µg/m² /dose, maximum daily dose 800-1000 µg) was administered q.d. or b.i.d. orally on day 1 followed by q.d. dosing concomitant with q.d. dosing of oral TMZ (20-55 mg/m² /day) on days 2 to 6, every 28 days.

Results

Forty patients, aged 4 to 25 years, were enrolled. Talazoparib was increased to 600 µg/m² /dose b.i.d. on

SUBMITTER: Schafer ES 

PROVIDER: S-EPMC9134216 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature